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|
| Type |
Symposium |
| Area |
Physical Chemistry of Bioimaging and Biospectroscopy |
| Room No. |
Room 208+209+210 |
| Time |
FRI 09:00-: |
| Code |
PHYS2-1 |
| Subject |
RNA Stem Structure Governs Coupling of Dicing and Gene Silencing in RNA interference |
| Authors |
Hye Ran Koh*, Amirhossein Ghanbariniaki1, Sua Myong1,*
Department of Chemistry, Chung-Ang University, Korea
1Department of Biophysics, Johns Hopkins University, United States
|
| Abstract |
Pre-micro(mi)RNAs possess secondary structures consisting of a loop and a stem with multiple mismatches. Despite the well characterized RNA interference (RNAi) pathway, it still remains unclear how the structural features of pre-miRNA contribute to dicing and subsequent gene silencing efficiency. Using single molecule fluorescence in situ hybridization, we demonstrate that cytoplasmic mRNA, but not nuclear mRNA, is reduced during RNAi. Dicing rate and silencing efficiency both increase as a function of the loop length in a correlated manner. In contrast, mismatches in the stem drastically diminish the silencing efficiency without impacting the dicing rate. We show that such decoupling effect is not due to the loading to RNA induced silencing complex, RNA uptake or cellular dicing. We postulate that the stem mismatches perturb the hand-over of the cleaved miRNAs from Dicer to Argonaute which leads to poor strand selection. Our results imply that the stem structures prevalent in cellular miRNAs are intended for suboptimal silencing efficiency. |
| E-mail |
hrankoh@gmail.com |
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120th General Meeting of the KCS